Project Summary/Abstract National guidelines direct nephrologists to refer patients with advanced kidney disease for placement of arteriovenous (AV) fistulas as the vascular access of choice for hemodialysis, instead of AV grafts. These guidelines were based on retrospective and observational analyses done nearly two decades ago among patients with a mean age of 59.4 years. Currently, adults 70 years of age and older comprise nearly 30% of patients with end-stage kidney disease compared to less than 15% two decades ago. Importantly, AV access placement may adversely impact upper extremity strength and function, and AV fistulas may cause greater deficits in overall physical function due to lengthier time to develop compared with AV grafts; grafts have better patency rates and can be used faster. Changes in physical abilities (i.e., precipitous decline in physical performance and self-sufficiency) are prevalent in older patients commencing hemodialysis, making the lack of data on the functional impact of initial AV access strategy (fistulas or grafts) even more critical. This GEMSSTAR proposal is focused on older patients with incident end-stage kidney disease with no prior vascular access surgery. We will randomly allocate patients undergoing hemodialysis via a tunneled catheter to either graft-first (intervention) or fistula-first (comparator) placement. Patient-centered functional outcomes (upper extremity strength, gait speed, independence and quality of life) and vascular access outcomes (AV access primary patency rate) will be compared. Our scientific premise: graft-first placement will yield higher rates of functional access, fewer following procedures to aid access development, and faster transition from catheter to AV access use; these will translate into higher patient satisfaction in the graft-first group. Our first hypothesis is that AV access placement will have adverse consequences on upper extremity function, mediated by the degree of preoperative muscle strength. We anticipate that the fistula-first strategy will have a greater negative impact on upper extremity physical function than the graft-first strategy. Our second hypothesis is that the success rate of AV access approach (i.e., primary AV access patency) will correlate with patient-reported outcomes for quality of life. The results of this study will provide critically needed data on the relationship between initial AV access approach and outcomes important to health and quality of life in older patients including the role of muscle strength in vascular access outcomes. Data from this pilot study will guide the design, conduct, and sample size for a subsequent multicenter study comparing AV fistulas to grafts in older adults with advanced chronic kidney disease, with the overarching objective of identifying strategies that decrease AV access failure rates and improve patients' quality of life. The applicant seeks to augment her expertise in clinical research with gerontology and geriatric specific training and expert mentoring to become a leader in geriatric nephrology research and improve outcomes among the growing numbers of older Americans with kidney disease. 1